How AVID should we be about the latest amyloid-based biomarker findings?

How enthusiastic should we be about the latest news from the FDA that one of their panels voted to endorse (with caveats) florbetapir (AVID-45) as a potential PET amyloid imaging agent in living patients? Even the Alzheimer’s Association, while on the one hand said it was onlypositive news, reminded us that plaques in the brain are not the same as Alzheimer’s.

The committee itself was concerned about whether the scans could be read accurately outside a research study, so they recommended additional work before approval. At the same time the head of the association’s advisory board reminded us that such tests are expensive and invasive. He said this while discussing the results of another study published in JAMA at the same time as the imaging study. In this work investigators examined the amount of amyloid in the blood plasma. There appeared to be some weak association between low levels and cognitive impairment but only in some circumstances depending on the patient’s level of education and ApoE gene status.

Everyone seems to realize this test is not ready for prime time.

An accompanying editorial suggested neither approach was ready for clinical use. Despite the less credible enthusiasm of the New York Times what we really learn from these studies is the difficulty of making the measurements, the lack of association between amyloid and dementia in many cases, and the heterogeneity of the process we still try to call one disease.

And finally we are always reminded by the experts (particularly those with connections to drug companies) that we need these tests so we can identify people at risk early so we can give the powerful treatments as soon as possible. Which treatments you ask? I should have said powerfully promised treatments. Our group is off the the national meeting of the Alzheimer’s Disease Cooperative Study (big drug trials group funded by NIH) this weekend. I doubt the magic bullet answer will be found this weekend nor on any other weekend (or weekday) I am afraid.

The really positive news for families affected by dementia will come when a bit more honestly enters the field and we lose the false hope that money, drug companies, and scientists will produce answers for everything.

This new development is indeed remarkable. First, it should be said that I do agree with the authors quoted by NY Times reporter Gina Kolata that accurate diagnosis of AD (or conversely, ruling it out) would be a “tremendous advance from the standpoint of care planning,” and certainly not just because it would save lots of money…

Secondly: However ‘promising’ my first point may be, as we all know this moves us no closer to treatments that would cure or even forestall AD. Personally and professionally I don’t believe it is possible to develop an effective treatment once each (unique) person has developed enough beta amyloid to begin showing symptoms. Common sense and some basic knowledge about human brain function, and the location of specific sites relating to specific functions should tell us that the quantity, quality, and location of amyloid deposits may vary significantly from person to person, thus affecting the organic brain tissue in significantly different ways, thus affecting the quality and severity of symptoms expressed by a given individual. And even that is not the end of the story…

Thirdly, each person has his/her unique personal/biological history. For example, how did your unique set of genes determine the actual shape and function of your unique brain as it developed? What other possible damage co-exists (from 50, 60, 70 or more years of living and all habits/accidents/life stress accumulation, etc) along WITH the amyloid deposits, and how does this complex mixture combine to create any particular mix in any particular, unique individual? Or, what psychotropic medications have been added to this soup, and for how long?

Psychotropic medications, though varying in strength, are not now, and may never be, tailored to any unique individual’s brain chemistry and neuronal structure. This would obviously be enormously costly (at least at current costs for developing new drugs) even if it were possible. The daunting complexity of even attempting to accomplish such feats would certainly be prohibitive given the current level of sophistication of our biomedical sciences.

Finally, what potential side effects might arise simply from the diagnostic procedure (radiopharmaceutical dye scanning) described below? There was no mention of this that I could find in the article. Are they THAT confident that this procedure has no side effects? Hard to believe…

This is all just my focused opinion. I would love to hear what others think, either about my comments or the Times article. And as always, thank you, Peter, for your critical and insightful appraisals.

I am doubtful and also hope that the test does not move into practice quickly. Having the FDA approve something is not tantamount to clinical use. It really offers very little information to people about prognosis or treatment options. Do remember that amyloid burden does not equate to Alzheimer’s or even having a dementia? Cost has not even been mentioned in the publicity. I agree with Charles that this test has no implications for current treatment and I think little real to contribute to future ways to improve quality if life. The notion of personalized medicine seems quite unrealistic even scientifically, particularly in this economic climate.